HEPATITISHEPATITIS

Khalid BzeiziKhalid Bzeizi

What Is Hepatitis?What Is Hepatitis?

The word "The word "hepatitishepatitis" means inflammation of the " means inflammation of the liverliver. Toxins, certain drugs, some diseases, . Toxins, certain drugs, some diseases, heavy alcohol use, bacterial and viral infections heavy alcohol use, bacterial and viral infections can all cause hepatitis. can all cause hepatitis.

HepatitisHepatitis

Drug Induced HepatitisDrug Induced Hepatitis

Autoimmune HepatitisAutoimmune Hepatitis

ClassicalClassical

Anti LKMAnti LKM

Anti SLA Anti SLA

Viral HepatitisViral Hepatitis

Common viruses cause hepatitis include Common viruses cause hepatitis include A,B,C,D,EA,B,C,D,E

Viral Hepatitis: Hepatitis A through E (more than Viral Hepatitis: Hepatitis A through E (more than 95% of viral cause).95% of viral cause).

Herpes simplex, Cytomegalovirus, Epstein-Barr, Herpes simplex, Cytomegalovirus, Epstein-Barr, yellow fever virus, adenoviruses.yellow fever virus, adenoviruses.

Hepatitis AHepatitis A

AAn acute liver disease caused by the n acute liver disease caused by the hepatitis A virus (HAV), hepatitis A virus (HAV),

Duration: few weeks to several months. Duration: few weeks to several months.

It does not lead to chronic infection.It does not lead to chronic infection.

Hepatitis A Virus

Transmission of HAVTransmission of HAV

Ingestion of food or water contaminated Ingestion of food or water contaminated with faecal matterwith faecal matter

Clinical ManifestationsClinical Manifestations

Incubation period 2 – 6 weeksIncubation period 2 – 6 weeks May be asymptomaticMay be asymptomatic Overt illness in 5%Overt illness in 5% Present as two stages,Present as two stages,

1 Preicteric1 Preicteric

2 Icteric2 Icteric

Clinical featuresClinical features

MalaiseMalaise AnorexiaAnorexia Nausea, vomittingNausea, vomitting liver tendernessliver tenderness Onset of JaundiceOnset of Jaundice Recovery in 4-6 weeksRecovery in 4-6 weeks Mortality 0.1 – 1 %Mortality 0.1 – 1 %

Complications: Fulminant hepatitisCholestatic

hepatitisRelapsing

hepatitis

Chronic sequelae: None

Hepatitis A - Clinical Complications

Laboratory DiagnosisLaboratory Diagnosis

Acute infection is diagnosed by the detection of HAV-IgM Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA.in serum by EIA.

Past Infection i.e. immunity is determined by the detection Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.of HAV-IgG by EIA.

Cell culture – difficult and take up to 4 weeks, not Cell culture – difficult and take up to 4 weeks, not routinely performedroutinely performed

Direct DetectionDirect Detection – EM, RT-PCR of faeces. Can – EM, RT-PCR of faeces. Can detect illness earlier than serology but rarely detect illness earlier than serology but rarely performed.performed.

FecalHAV

Symptoms

0 1 2 3 4 5 6 12

24

Hepatitis A Infection

Total anti-HAV

Titer ALT

IgM anti-HAV

Months after exposure

Typical Serological Course

TreatmentTreatment

No specific antiviral drug is availableNo specific antiviral drug is available Treatment is symptomaticTreatment is symptomatic Specific passive prophylaxis by pooled Specific passive prophylaxis by pooled

normal human immunoglobulin given normal human immunoglobulin given before exposure or in early incubation before exposure or in early incubation period can prevent or attenuate clinical period can prevent or attenuate clinical illness.illness.

Vaccination for HAVVaccination for HAV Hepatitis A vaccination is recommended for all Hepatitis A vaccination is recommended for all

children starting at age 1 year, travellers to children starting at age 1 year, travellers to certain countries, and others at risk. certain countries, and others at risk.

A full course containing two intramuscular A full course containing two intramuscular injections of the vaccineinjections of the vaccine

Protection starts after 4 weeks after injection Protection starts after 4 weeks after injection and lasts for 10 – 20 yearsand lasts for 10 – 20 years

Hepatitis B Hepatitis B InfectionInfection

Hepatitis BHepatitis B

Causative agent: Double stranded DNA virus. Causative agent: Double stranded DNA virus.

Ranges in severity from a mild illness, lasting Ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term a few weeks (acute), to a serious long-term (chronic) illness that leads to cirrhosis and/or (chronic) illness that leads to cirrhosis and/or liver cancer. liver cancer.

Most Important Infectious Most Important Infectious DiseaseDisease

There are more than 350 million carriersThere are more than 350 million carriers

25% of them will develop chronic active 25% of them will develop chronic active hepatitis.hepatitis.

World wide 1 million deaths a year are World wide 1 million deaths a year are attributed to HBV related liver disease and attributed to HBV related liver disease and Hepatocellular CarcinomaHepatocellular Carcinoma

Transmission of HBV

Horizontal Transmission

Child-to-ChildContaminated Needles

SexualHealth Care Worker

TransfusionHemodialysis

Vertical Transmission

Perinatal

CDC Fact Sheet. http://www.cdc.gov/ncidod/diseases/hepatitis/b/. Lee. N Engl J Med. 1997;337(24):1733-1745.Lavanchy. J Viral Hepat. 2004;11(2):97-107.

Common in regions with HBsAg

prevalence of > 2%

Incubation period: Average 60-90 days

Clinical illness (jaundice): <5 yrs, <10%5 yrs, 30%-50%

Acute case-fatality rate: 0.5%-1%

Chronic infection: <5 yrs, 30%-90%5 yrs, 2%-10%

Hepatitis B - Clinical Features

DiagnosisDiagnosis A battery of serological tests are used for the diagnosis of A battery of serological tests are used for the diagnosis of

acute and chronic hepatitis B infection.acute and chronic hepatitis B infection. HBsAgHBsAg - used as a general marker of infection. - used as a general marker of infection. HBsAb HBsAb - used to document recovery and/or immunity to - used to document recovery and/or immunity to

HBV infection.HBV infection. anti-HBc IgManti-HBc IgM - marker of acute infection. - marker of acute infection. anti-HBcIgGanti-HBcIgG - past or chronic infection. - past or chronic infection. HBeAgHBeAg - indicates active replication of virus and therefore - indicates active replication of virus and therefore

infectiveness.infectiveness. Anti-HbeAnti-Hbe - virus no longer replicating. However, the - virus no longer replicating. However, the

patient can still be positive for HBsAg which is made by patient can still be positive for HBsAg which is made by integrated HBV.integrated HBV.

HBV-DNAHBV-DNA - indicates active replication of virus, more - indicates active replication of virus, more accurate than HBeAg especially in cases of escape accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.mutants. Used mainly for monitoring response to therapy.

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Weeks after Exposure

Titre

IgM anti-HBc

Total anti-HBc

HBsAg

Acute(6 months)

HBeAg

Chronic(Years)

anti-HBe

0 4 8 12 16 20 24 28 32 36 52 Years

Weeks after Exposure

Titre

Progression to Chronic Hepatitis B Virus InfectionTypical Serologic Course

Sexual - sex workers and homosexuals are particular at risk.

Parenteral - IVDA, Health Workers are at increased risk.

Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.

Hepatitis B Virus

Modes of Transmission

Disease Progression Occurs in15% to 40% of Chronic HBV Patients

TreatmentTreatment Interferon Interferon

Lamivudine Lamivudine

..

Adefovir Adefovir

Entecavir Entecavir

Tenofovir Tenofovir

Vaccination Genetically Vaccination Genetically EngineeredEngineered

VaccinationVaccination - highly effective - highly effective recombinant vaccines are now available. recombinant vaccines are now available. Vaccine can be given to those who are Vaccine can be given to those who are at increased risk of HBV infection such at increased risk of HBV infection such as health care workers. It is also given as health care workers. It is also given routinely to neonates as universal routinely to neonates as universal vaccination in many countries.vaccination in many countries.

Hepatitis B ImmunoglobulinHepatitis B Immunoglobulin

Hepatitis B ImmunoglobulinHepatitis B Immunoglobulin - HBIG may be - HBIG may be used to protect persons who are exposed to used to protect persons who are exposed to hepatitis B. It is particular efficacious within hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given 48 hours of the incident. It may also be given to neonates who are at increased risk of to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positiveHBsAg and HBeAg positive

Hepatitis C InfectionHepatitis C Infection

What is Hepatitis C VirusWhat is Hepatitis C Virus

Hepatitis C virus was also known as Non Hepatitis C virus was also known as Non A or Non B virus found while doing A or Non B virus found while doing experiments on Chimpanzees.experiments on Chimpanzees.

HCV infections are seen only in humansHCV infections are seen only in humans

The epidemiology is like HBV infection.The epidemiology is like HBV infection.

hypervariableregion

capsid envelope

protein

protease/helicase

RNA-dependent

RNA polymerase

c22

5’

core

E1 E2 NS2

NS3

33c

NS4

c-100

NS5

3’

Hepatitis C Virus

Incubation period: Average 6-7

wksRange 2-26 wks

Clinical illness (jaundice): 30-40% (20-30%)

Chronic hepatitis: 70%

Persistent infection: 85-100%

Immunity: No protective antibody

response identified

Hepatitis C - Clinical Features

Hepatitis C virusHepatitis C virus

Six genotypes are identifiedSix genotypes are identified..

In Saudi Arabia, genotype 4 accounts In Saudi Arabia, genotype 4 accounts for around 65% of cases and genotype 1 for around 65% of cases and genotype 1 around 25%.around 25%.

Genotypes 1 and 4 are relatively more Genotypes 1 and 4 are relatively more difficult to treat compared to genotypes difficult to treat compared to genotypes 2 & 3.2 & 3.

How HCV transmittedHow HCV transmitted

Blood transfusionsBlood transfusions Transplantation of organsTransplantation of organs Injectable drug abusers Injectable drug abusers Immunocompromised Immunocompromised Sexual transmission ?Sexual transmission ? Less importantLess important Vertical transmission is possibleVertical transmission is possible

Clinical features Clinical features

Overt Jaundice is seen in 5% of patientsOvert Jaundice is seen in 5% of patients

About 50 – 80% patients progress to About 50 – 80% patients progress to

chronic hepatitischronic hepatitis

May progress to Cirrhosis, or Hepatocellular May progress to Cirrhosis, or Hepatocellular carcinomacarcinoma

Laboratory DiagnosisLaboratory Diagnosis

HCV antibodyHCV antibody - generally used to diagnose hepatitis C - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.weeks after infection before antibody appears.

ELISA test results to be confirmed with Immunoblotting ELISA test results to be confirmed with Immunoblotting assayassay

HCV-RNAHCV-RNA

HCV TreatmentHCV Treatment

Pegylated Pegylated InterferonInterferon RibavirinRibavirin DAAsDAAs

No vaccineNo vaccine

Hepatitis D VirusHepatitis D Virus

The delta agent is a defective virus which shows The delta agent is a defective virus which shows similarities with the viroids in plants. similarities with the viroids in plants.

The agent consists of a particle 35 nm in diameter The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer consisting of the delta antigen surrounded by an outer coat of HBsAg.coat of HBsAg.

The genome of the virus is very small and consists of a The genome of the virus is very small and consists of a

single-stranded RNA single-stranded RNA

Coinfection– severe acute disease.– low risk of chronic infection.

Superinfection– usually develop chronic HDV infection.– high risk of severe chronic liver disease.– may present as an acute hepatitis.

Hepatitis D - Clinical Features

Hepatitis E VirusHepatitis E Virus

Calicivirus-like virusesCalicivirus-like viruses unenveloped RNA virus, 32-34 nm in unenveloped RNA virus, 32-34 nm in

diameterdiameter +ve stranded RNA genome, 7.6 kb in size.+ve stranded RNA genome, 7.6 kb in size. very labile and sensitivevery labile and sensitive Can only be cultured recentlyCan only be cultured recently

Incubation period: Average 40 days

Range 15-60 days Case-fatality rate: Overall, 1%-3%

Pregnant women, 15%-25%

Illness severity: Increased with age

Chronic sequelae: None identified

Hepatitis E - Clinical Features

Most outbreaks associated with faecally contaminated drinking water.

Several other large epidemics have occurred since in the Indian subcontinent and the USSR, China, Africa and Mexico.

Minimal person-to-person transmission.

Hepatitis E - Epidemiologic

Features